PARTNERS WITH
Pembrolizumab
Immune check point inhibitors (ICPIs)
MECHANISM OF ACTION
Tumor cells evade immunosurveillance by activating immune checkpoint pathways that suppress antitumor immune responses; ICPis release the brakes on the immune system, promoting antitumor immune responses by interrupting co-inhibitory signaling pathways and promoting immune-mediated elimination of tumor cells.
Target PDL-1
MECHANISM OF KIDNEY INJURY
AIN (Acute interstitial nephritis), ATN (Acute tubular necrosis), Water/electrolyte disturbances, Glomerular injury, Tubular injury, Podocyte Injury, Chronic interstitial Nephritis
CLINICAL KIDNEY SYNDROME
AKI, Proteinuria/Albuminuria, Nephrotic syndrome, Rhabdomyolysis
Extra-renal, ILD, AIN, colitis, hypophysitis, rash
CARDIOVASCULAR ADVERSE EFFECTS
Acute MI, Immune mediated myocarditis, pericarditis, vasculitis, cardiac ventricular arrhythmia, peripheral edema , pericardial effusion, cardiac tamponade -PMID: 25901283, PMID: 34680365, PMID: 30993259
LYTE ABNORMALITIES
Metabolic acidosis (HAGMA, NAGMA), Hypoalbuminemia, Nephrotic range protenuria, Hyponatremia, Hypokalemia, Hypophosphatemia
RISK FACTORS
PPI use, combination therapy, lower baseline eGFR, history of extrarenal irAEs
MITIGATION STRATEGIES
Early steroid use, stopping PPIs
SUGGESTIONS
Hold offending drug and rechallenge after AKI/proteinuria resolves, Discontinue offending drug, Treat with steroids taper
NOTES/COMMENTS
eGFR < 60 ml/min, no dose adjustment
PHARMACOKINETICS
Molecular Weight
149 kDa
Volume of Distribution
6 L
Plasma Protein Binding
Metabolism
No formal studies; but likely catabolism to small peptides and amino acids via protein degradation
Bioavailability
---
Half-life elimination
22 days
Time to peak
---
Excretion
No formal studies
Dialyzable?
No
REF:
Gupta JITC 2021, Seethapathy CJASN 2020, Cortazar JASN 2020
PATHOLOGY SLIDES:
ENTRY UPDATES:
Shruti Gupta
United States
Sep 25, 2022